An ecological framework to understand the efficacy of fecal microbiota transplantation.
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ABSTRACT:
SUBMITTER: Xiao Y
PROVIDER: S-EPMC7334230 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEstablishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.ResultsSpecifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor-recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.ConclusionsOverall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. Video abstract.
| S-EPMC8858662 | biostudies-literature
Project description:Few studies have been conducted on the attitudes of patients seeking fecal microbiota transplantation (FMT). This study aimed to investigate the reasons for patients with Crohn's disease (CD) seeking FMT and their attitude changes after FMT.In this prospective study, all included patients were diagnosed with CD for at least 6 months and intended to receive FMT. A questionnaire was designed to investigate the history of medical visits and patients' attitudes toward FMT. Only refractory patients who failed to clinically respond to previous treatment were selected for undergoing FMT. Three months after the first FMT, patients were required to complete the second questionnaire on attitudes toward the first FMT.A total of 207 patients with CD were included for questionnaire survey. In 118 refractory patients, 94.07% sought FMT because they had no other choice. In 89 nonrefractory patients, 78.65% sought FMT for the reason that they wanted to achieve better clinical results or even a cure, although the current treatment was effective for them. In all, 118 refractory patients received FMT. Three months after the first FMT, 88.98% (105/118) patients completed the questionnaire on patients' attitudes toward FMT. Of these 105 patients, 56.19% reported to have satisfactory clinical efficacy and 74.29% were willing to receive the second FMT. Moreover, 89.52% (94/105) showed their willingness to recommend FMT to other patients.In conclusion, this study at least first time demonstrated that patients with CD were willing to accept FMT due to its efficacy.
| S-EPMC5265816 | biostudies-literature
Project description:Background & aimsFecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.MethodsWe performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.ResultsOf 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.ConclusionsBased on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.
| S-EPMC7549313 | biostudies-literature
Project description:ObjectiveTo study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice.MethodWe measured the severity of disease by clinical EAE scores and H&E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs.ResultsWe observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37.ConclusionAltogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.
| S-EPMC8687821 | biostudies-literature
Project description:Fecal microbiota transplantation is being assessed as a treatment for chronic microbiota-related diseases such as ulcerative colitis. Results from an initial randomized trial suggest that remission rates depend on unobservable features of the fecal donors and observable features of the patients. We use mathematical modeling to assess the efficacy of pooling stools from different donors during multiple rounds of treatment. In the model, there are two types of patients and two types of donors, where the patient type is observable and the donor type (effective or not effective) is not observable. In the model, clinical outcomes from earlier rounds of treatment are used to estimate the current likelihood that each donor is effective, and then each patient in each round is treated by a pool of donors that are currently deemed to be the most effective. Relative to the no-pooling case, pools of size two or three significantly increase the proportion of patients in remission during the first several rounds of treatment. Although based on data from a single randomized trial, our modeling suggests that pooling of stools - via daily cycling of encapsulated stool from several different donors - may be beneficial in fecal microbiota transplantation for chronic microbiota-related diseases.
| S-EPMC5221766 | biostudies-literature
Project description:The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.
| S-EPMC9184500 | biostudies-literature
Project description:Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis associated diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD). The engraftment of donor bacteria is essential for the effectiveness of FMT, which to some extent depends on the matching of donors and recipients. However, how different types of donor-derived bacteria affect FMT efficacy has not been fully dissected. We recruited two longitudinal IBD cohorts of 103 FMT recipients and further analyzed 1,280 microbiota datasets from 14 public CDI and IBD studies to uncover the effect of donor-derived microbiota in recipients. We found that two enterotypes, RCPT/E and RCPT/B (dominated by Enterobacteriaceae and Bacteroides, respectively), consistently exist in both CDI and IBD patients. Based on a time-course-based multi-cohort analysis of FMT fecal samples, we observed the interplay between recipient and donor-derived microbiota during FMT, in which the FMT outcome was significantly associated with the enterotype and microbiota distance between donor and recipient after FMT. We proposed a new measurement, the ratio of colonizers to residents after FMT (C2R), to quantify the engraftment of donor-derived bacteria in the recipients, and then constructed an enterotype-based statistical model for donor-recipient matching, which was validated by both cross-validation and an additional IBD FMT cohort (n = 42). We believe that with the accumulation of FMT multi-omics datasets, machine learning-based methods will be helpful for rational donor selection for improving efficacy and precision FMT practices.
| S-EPMC9302524 | biostudies-literature
Project description:Background and Aims: Due to increasing knowledge of the "gut-liver axis", there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available.
| S-EPMC9311594 | biostudies-literature
Project description:BackgroundThere is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation.MethodsA 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data.ResultsAll 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL.InterpretationThe experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.
| S-EPMC7869690 | biostudies-literature
Project description:This article discusses the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The disruption of the normal gut microbiota is central to the pathogenesis of CDI, and disruption persists in recurrent disease. The use of FMT for recurrent CDI is characterized by a high response rate and short term safety is excellent, although the long-term effects of FMT are as yet unknown.
| S-EPMC4328137 | biostudies-other